Fracture risk associated with osteoporosis represents a concern that is likely to become ever more serious as the nation's population ages. The FDA has approved 7 drugs designed to slow or reverse osteoporosis. The gold standard for monitoring pharmacological treatment is Dual Energy X-ray Absorptiometry (DEXA), which provides a measure of bone mineral density (BMD). In principle, bone sonometry is capable of providing additional information regarding bone quality because it is sensitive not only to bone mineral density but also to microstructure and orientation which influence fracture risk. In spite of its promise, however, sonometry has not yet been shown to provide such additional bone quality information, in part because of the specific limitations to be addressed in the proposed research. Phase cancellation at the receiving transducer has a negative impact on bone sonography. Transmission of ultrasound through bone is results in the generation of multiple modes of propagation including fast and slow waves, mode convertion, and multiple scattering - effects that can mask the underlying material properties of bone that determine fracture risk. At present, sonometry is limited to sites permitting through transmission such as the cancaneus, whereas sites at highest risk of fracture such as the hip would be accessible only to backscattered ultrasound. We have therefore identified three specific aims: 1) Identify, segregate, and overcome limitations of current transmission-based calcaneus sonometry arising from phase cancellation at the receiving transducer, 2) implement Bayes inversion of the ultrasonic signals to estimate the underlying bone material properties from received transmission sonometry signals complicated by the presence of multiple modes, and 3) validate, expand, and refine methods for estimating fracture risk in high risk sites such as the hip based on backscattered ultrasound. The long-term goal of the proposed research is to enhance and expand bone sonometry to facilitate its role in monitoring bone quality and the potential regression of osteoporosis with the aid of pharmacological interventions. PUBLIC HEALTH RELEVANCE: Osteoporotic fractures reduce quality of life and carry enormous health care costs. Sonometry could improve bone quality assessment because, unlike DEXA, it is sensitive to bone microstructure and orientation. The proposed research addresses fundamental improvements to existing sonometry techniques, and explores new techniques applicable to the hip and spine that are at relatively high risk of fracture but currently cannot be monitored.